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Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation

Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to un...

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Autores principales: Pende, Daniela, Falco, Michela, Vitale, Massimo, Cantoni, Claudia, Vitale, Chiara, Munari, Enrico, Bertaina, Alice, Moretta, Francesca, Del Zotto, Genny, Pietra, Gabriella, Mingari, Maria Cristina, Locatelli, Franco, Moretta, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558367/
https://www.ncbi.nlm.nih.gov/pubmed/31231370
http://dx.doi.org/10.3389/fimmu.2019.01179
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author Pende, Daniela
Falco, Michela
Vitale, Massimo
Cantoni, Claudia
Vitale, Chiara
Munari, Enrico
Bertaina, Alice
Moretta, Francesca
Del Zotto, Genny
Pietra, Gabriella
Mingari, Maria Cristina
Locatelli, Franco
Moretta, Lorenzo
author_facet Pende, Daniela
Falco, Michela
Vitale, Massimo
Cantoni, Claudia
Vitale, Chiara
Munari, Enrico
Bertaina, Alice
Moretta, Francesca
Del Zotto, Genny
Pietra, Gabriella
Mingari, Maria Cristina
Locatelli, Franco
Moretta, Lorenzo
author_sort Pende, Daniela
collection PubMed
description Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell function and the molecular mechanisms of tumor cell killing. Stemmed from the seminal discoveries in early ‘90s, in which Alessandro Moretta was the major actor, an extraordinary amount of research on KIR specificity, genetics, polymorphism, and repertoire has followed. These basic notions on NK cells and their receptors have been successfully translated to clinical applications, primarily to the haploidentical hematopoietic stem cell transplantation to cure otherwise fatal leukemia in patients with no HLA compatible donors. The finding that NK cells may express the PD-1 inhibitory checkpoint, particularly in cancer patients, may allow understanding how anti-PD-1 therapy could function also in case of HLA class I(neg) tumors, usually susceptible to NK-mediated killing. This, together with the synergy of therapeutic anti-checkpoint monoclonal antibodies, including those directed against NKG2A or KIRs, emerging in recent or ongoing studies, opened new solid perspectives in cancer therapy.
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spelling pubmed-65583672019-06-21 Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation Pende, Daniela Falco, Michela Vitale, Massimo Cantoni, Claudia Vitale, Chiara Munari, Enrico Bertaina, Alice Moretta, Francesca Del Zotto, Genny Pietra, Gabriella Mingari, Maria Cristina Locatelli, Franco Moretta, Lorenzo Front Immunol Immunology Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell function and the molecular mechanisms of tumor cell killing. Stemmed from the seminal discoveries in early ‘90s, in which Alessandro Moretta was the major actor, an extraordinary amount of research on KIR specificity, genetics, polymorphism, and repertoire has followed. These basic notions on NK cells and their receptors have been successfully translated to clinical applications, primarily to the haploidentical hematopoietic stem cell transplantation to cure otherwise fatal leukemia in patients with no HLA compatible donors. The finding that NK cells may express the PD-1 inhibitory checkpoint, particularly in cancer patients, may allow understanding how anti-PD-1 therapy could function also in case of HLA class I(neg) tumors, usually susceptible to NK-mediated killing. This, together with the synergy of therapeutic anti-checkpoint monoclonal antibodies, including those directed against NKG2A or KIRs, emerging in recent or ongoing studies, opened new solid perspectives in cancer therapy. Frontiers Media S.A. 2019-05-28 /pmc/articles/PMC6558367/ /pubmed/31231370 http://dx.doi.org/10.3389/fimmu.2019.01179 Text en Copyright © 2019 Pende, Falco, Vitale, Cantoni, Vitale, Munari, Bertaina, Moretta, Del Zotto, Pietra, Mingari, Locatelli and Moretta. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pende, Daniela
Falco, Michela
Vitale, Massimo
Cantoni, Claudia
Vitale, Chiara
Munari, Enrico
Bertaina, Alice
Moretta, Francesca
Del Zotto, Genny
Pietra, Gabriella
Mingari, Maria Cristina
Locatelli, Franco
Moretta, Lorenzo
Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation
title Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation
title_full Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation
title_fullStr Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation
title_full_unstemmed Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation
title_short Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation
title_sort killer ig-like receptors (kirs): their role in nk cell modulation and developments leading to their clinical exploitation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558367/
https://www.ncbi.nlm.nih.gov/pubmed/31231370
http://dx.doi.org/10.3389/fimmu.2019.01179
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